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CLINICAL STATEMENTS AND GUIDELINES Circulation. 2023;148:e9–e119. DOI: 10.1161/CIR.0000000000001168 August 29, 2023 Virani et al 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guideline is based on historical data with warfarin as well as data extrapolated from more recent studies evaluating various combination therapies versus monotherapy in patients with a recent ACS.38-44,66–70 15 The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial evaluated the efficacy and safety of low-dose rivaroxaban 2.5 mg twice daily, with or without low-dose aspirin therapy, in reducing CVD events in patients with stable ASCVD.30 The primary outcome of cardiovascular death, stroke, or MI occurred in 4.1% of the aspirin plus rivaroxaban group, 4.9% of the rivaroxaban alone group, and 5.4% for aspirin monotherapy. The study was terminated early because of the observed benefit of rivaroxaban plus aspirin compared with aspirin alone. Evaluation of high-risk patients (multivessel CAD and at least one of the following: diabetes requiring medication, recurrent MI, peripheral artery disease, HF, or CKD with an eGFR of 15-59 mL/min/m2 69) showed an absolute net clinical benefit with combination therapy, with substantial reductions in ischemic events and all-cause death.31 The high-risk population also derived a larger absolute risk reduction, resulting in an even lower number needed to treat.30–32 The combination of rivaroxaban plus aspirin resulted in a higher risk of major bleeding compared with aspirin monotherapy (3.1% versus 1.9%; hazard ratio, 1.70 [95% CI, 1.40–2.05]; P<0.001]). The use of DAPT was an exclusion criteria. 16. Increased bleeding including gastrointestinal bleeding is a common side effect of DAPT; the mitigation of this risk has been an area of clinical investigation. SAPT (aspirin or clopidogrel) compared with DAPT leads to lower gastric or small intestinal mucosal injury.71 Aspirin increases gastroduodenal ulcer formation. When combined with aspirin therapy, P2Y12 inhibitors can promote gastric ulcer bleeding. Clopidogrel is a prodrug that requires cytochrome CYP P450 2C19 for metabolism to its active form. PPIs are also metabolized by the P450 system, thereby leading to concern for inadequate clopidogrel therapy in those on both PPIs and DAPT. The FDA has added a boxed warning to avoid use of omeprazole with clopidogrel as well as other potent CYP 2C19 inhibitors, including esomeprazole. Several studies assessed the safety and efficacy of PPI in the context of DAPT. A meta-analysis of 6 RCTs (6930 patients) showed that the use of PPIs is associated with a reduced risk of gastrointestinal bleeding in patients treated with DAPT after PCI. No significant differences were observed in the incidence of MACE, MI, and all-cause death in patients with CAD on DAPT and PPIs.33 4.3.2 Beta Blockers Recommendations for Beta Blockers Referenced studies that support the recommendations are summarized in the Online Data Supplement. COR LOE Recommendations 1 A 1 In patients with CCD and LVEF ≤40% with or without previous MI, the use of beta-blocker therapy is recommended to reduce the risk of future MACE, including cardiovascular death.1–3 1 A 2 In patients with CCD and LVEF <50%, the use of sustained release metoprolol succinate, carvedilol, or bisoprolol with titration to target doses is recommended in preference to other beta blockers.*1,3–8 2b B-NR 3 In patients with CCD who were initiated on beta- blocker therapy for previous MI without a history of or current LVEF ≤50%, angina, arrhythmias, or uncontrolled hypertension, it may be reasonable to reassess the indication for long-term (>1 year) use of beta-blocker therapy for reducing MACE.9–15 3: No Benefit B-NR 4 In patients with CCD without previous MI or LVEF ≤50%, the use of beta-blocker therapy is not beneficial in reducing MACE, in the absence of another primary indication for beta-blocker therapy.†16–19 *Modified from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.20 †Adapted from the 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.21 Synopsis Beta blockers exhibit their clinical effects by decreasing myocardial oxygen demand, improving ischemic threshold, and impeding maladaptive LV remodeling.1,22–24 Patients with CCD comprise patients with or without previous MI, LV systolic dysfunction, or both. These distinctions should be considered in determining the indications for use of beta-blocker therapy in patients with CCD. The strongest data for the benefit of beta-blocker therapy in CCD is for patients with LV systolic dysfunction but is less clear for patients without LV dysfunction.1,3-8,13-15,25–27 Several ongoing RCTs hope to better elucidate the need for and duration of beta-blocker therapy for MACE reduction among post-MI patients with preserved LV systolic function in the contemporary era. Other primary indications for beta blockers may include their use for angina, uncontrolled hypertension, or arrhythmias. A comprehensive screening as well as assessment of their symptoms and comorbid conditions is recommended given that beta-blocker therapy may still be indicated for its antianginal properties (see Section 4.3.6), antihypertensive properties (see Section 4.2.7, “Blood Pressure Management”), or for its negative chronotropic effects among patients with rhythm disturbance disorders.28,29 Recommendation-Specific Supportive Text 1 Multiple well-conducted RCTs from the precontem- porary as well as modern era showed the efficacy of beta-blocker therapy in reducing cardiovascular Downloaded from http://ahajournals.org by on October 7, 2026